Acetic Acid → 4-Bromo-6-fluoro-1H-indole

HRID 475264

반응식

HRID 475264 반응식
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([N+:9]([O-])=O)[C:3]=1[CH3:12].N1CCC[CH2:14]1.CC(O)=O.[OH-].[Na+]>O1CCOCC1.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]2[C:3]=1[CH:12]=[CH:14][NH:9]2

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 27733851-Bromo-5-fluoro-2-methyl-3-nitrobenzene

생성물 1

HCID 247281734-Bromo-6-fluoro-1H-indole수율 27%

시약·촉매·용매 2

HCID 23925Iron촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a solution of 1-bromo-5-fluoro-2-methyl-3-nitrobenzene (4.69 g, 20 mmol) in 1,4-dioxane (25 mL) at RT was slowly added DMF dimethylacetal (13.3 mL) and pyrrolidine (1.7 mL). The solution was heated at 100° C. for 18 h, then concentrated in vacuo to give a dark residue. To the residue was added HOAc (30 mL) and iron powder (11 g, 200 mmol) then the mixture was heated to reflux for 1 h, cooled to RT, neutralized by addition of 50% aq. NaOH and extracted with EtOAc (2×200 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with an EtOAc/petroleum ether gradient (5 to 30% EtOAc) to afford 1.16 g (27%) of 4-bromo-6-fluoro-1H-indole (224)—as brown solid: MS (ESI) m/z=213.9 [M+1]+.

후처리

  1. customat RT
  2. concentrationconcentrated in vacuo
  3. customto give a dark residue
  4. temperaturethe mixture was heated
  5. temperatureto reflux for 1 h
  6. temperaturecooled to RT
  7. extractionextracted with EtOAc (2×200 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by SiO2 chromatography
  12. washeluting with an EtOAc/petroleum ether gradient (5 to 30% EtOAc)

출처 및 근거

ORD 기록
ord-952faae079564f3ab9268fba4e57f743
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637537B2

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